Learning Objectives: On successful completion of this activity, participants should be able to (1) describe the methods that have been used to quantify 18 F-FDG uptake in the lungs using dynamic PET; (2) discuss the interpretation of the outcomes from these methods; and (3) provide suggested considerations on quantification of 18 F-FDG uptake in the lungs for future studies.
Cabotegravir long-acting (LA) intramuscular (IM) injection is being investigated for HIV preexposure prophylaxis due to its potent antiretroviral activity and infrequent dosing requirement. A subset of healthy adult volunteers participating in a Phase I study assessing cabotegravir tissue pharmacokinetics underwent serial magnetic resonance imaging (MRI) to assess drug depot localization and kinetics following a single cabotegravir LA IM targeted injection. Methods: Eight participants (four men, four women) were administered cabotegravir LA 600 mg under ultrasonographic-guided injection targeting the gluteal muscles. MRI was performed to determine injection-site location in gluteal muscle (IM), subcutaneous (SC) adipose tissue and combined IM/SC compartments, and to quantify drug depot characteristics, including volume and surface area, on Days 1 (≤2 hours postinjection), 3 and 8. Linear regression analysis examined correlations between MRI-derived parameters and plasma cabotegravir exposure metrics, including maximum observed concentration (C max ) and partial area under the concentration-time curve (AUC) through Weeks 4 and 8. Results: Cabotegravir LA depot locations varied by participant and were identified in the IM compartment (n = 2), combined IM/SC compartments (n = 4), SC compartment (n = 1) and retroperitoneal cavity (n = 1). Although several MRI parameter and exposure metric correlations were determined, total depot surface area on Day 1 strongly correlated with plasma cabotegravir concentration at Days 3 and 8, C max and partial AUC through Weeks 4 and 8.
Healthy ageing to middle age is associated with diminishing sensitivity to meal ingestion of visual food cue-evoked activity in brain regions that represent the salience of food and direct food-associated behaviour. Reduced satiety sensing may have a role in the greater risk of obesity in middle age.
Background: Respiratory diseases are one of the leading causes of death worldwide, yet effective treatment options remain limited. Although inflammation is thought to be a key driver in the pathogenesis and progression of several lung diseases, the underlying molecular mechanisms of lung dysfunction remain poorly understood. Imaging techniques may help to further our understanding of the pathophysiology and facilitate the translation of novel therapies. Positron Emission Tomography (PET) is a functional imaging technique which has the potential to interrogate the underlying inflammatory response. We present a systematic review of the literature summarising the emerging PET radiotracers developed to quantify pulmonary inflammation. Method: We performed a systematic review using the following databases: Medline, Embase, Scopus, PubMed, Web of Science and Cochrane. We included articles between 1995 and 2019 for all studies using PET radiotracers to evaluate inflammatory response in the lung. From a total of 911 articles covering both animal and human studies, two reviewers selected papers based on the inclusion/exclusion criteria and extracted data from 68 articles selected. Results: 53 out of 68 papers, including both human and animal studies, were eligible for synthesis. Heterogenous study populations and differences in study design, image acquisition and analysis made data pooling unfeasible; instead, we provide a narrative synthesis. Conclusions: Currently, very few novel radiotracers targeting lung inflammation have crossed the translational gap from animal models to human studies. Nevertheless, our results highlight a handful of promising tracers which warrant further evaluation in humans. 18 F-FDG has been investigated most extensively; although 18 F-FDG is not a specific inflammatory tracer, human studies of several pulmonary diseases support its use as a biomarker for inflammation. Despite ongoing debate about the optimal analysis methodology for 18 F-FDG lung images, standardisation of image acquisition and analysis should help to improve confidence in research outcomes. PET radiotracers can provide quantitative, targeted biomarkers which relate to the activity of molecular pathways and may expedite development of specific anti-inflammatory drugs.
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